Randomized controlled trial of nalfurafine for refractory pruritus in hemodialysis patients

Abstract

Background

Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.

Methods

In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 μg, 2.5 μg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.

Results

A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 μg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 μg and placebo group was 8.81 mm (p = .110). Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5μg, 38.6% in 2.5 μg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.

Conclusions

Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

Keywords:

• Nalfurafine
• kappa opioid receptor agonist
• hemodialysis
• refractory
• clinical trial
• chronic kidney disease-associated pruritus

Acknowledgments

The investors wish to acknowledge the financial support from Shenyang Sunshine Pharmaceuticals CO., Ltd to finish the study.

Author contributions

Zhang Ping and Xiang Shilong contributed equally to this manuscript. Zhang Ping and Chen Jianghua made substantial contributions to the conception and design of the work. Xiang Shilong drafted the manuscript. Zhang Ping and Xiang Shilong contributed to data analysis. Zhang Ping contributed to data interpretation. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. All authors contributed to the article and approved the submitted version. The following doctors participated in this prospective double-blind study: Liu Bicheng, Wang Xiaohui, Yang Xiaoping, Ye Chaoyang, Wang Zunsong, Li Yanlin, Li Zhou, Wang Caili, Li Hongbo, Huang Jian, Peng Ai, Wang Xiaoping, Wang Deguang, Xiao Jie, Chen Wenli, Cheng Hong, Mao Nan, Wang Jianqin, Yang Lin.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was also supported by research programs from the National Natural Science Foundation of China (81900694) and the Zhejiang Provincial Science and Technology Foundation of China (2021E50001). The clinical trial was registered on clinical trial (https://clinicaltrials.gov/show/NCT04728984, grant number NCT04728984) and China drug trials (http://www.chinadrugtrials.org.cn, grant number: CTR20201271).